Evaluating steady-state resting energy expenditure using indirect calorimetry in adults with overweight and obesity.

BACKGROUND: Determining a period of steady state (SS) is recommended when estimating resting energy expenditure (REE) using a metabolic cart. However, this practice may be unnecessarily burdensome and time-consuming in the research setting. AIM: The aim of the study was to evaluate the use of SS criteria, and compare it to alternative approaches in adults with overweight and obesity. METHODS: In this cross-sectional, ancillary analysis, participants enrolled in a bariatric (study 1; n = 13) and lifestyle (study 2; n = 51) weight loss intervention were included. Indirect calorimetry was performed during baseline measurements using a metabolic cart for 25 min, including a 5-min stabilization period at the start. SS was defined as the first 5-min period with a coefficient of variation (CV) ≤10% for both VO2 and VCO2 (hereafter REE5-SS). Body composition was measured using bioelectrical impedance analysis in study 2 participants only. REE5-SS was compared against the lowest CV (REECV-lowest), 5-min time intervals (REE6-10, REE11-15, REE16-20, REE21-25), 4-min and 3-min SS intervals (REE4-SS and REE3-SS), and time intervals of 6-15, 6-20 and 6-25 min (REE6-15, REE6-20, and REE6-25) using repeated measures ANOVA and Bland-Altman analysis to test for bias, limits of agreement and accuracy (±6% measured REE). RESULTS: Participants were 54 ± 13 years old, mostly women (75%) and had a BMI of 35 ± 5 kg/m2. Overall, 54/63 (84%) of participants reached REE5-SS, often (47/54, 87%) within the first 10-min (6-15 min). Alternative approaches to estimating REE had a relatively low bias (-16 to 13 kcals), narrow limits of agreement and high accuracy (83-98%) when compared to REE5-SS, in particular, outperforming standard prediction equations (e.g., Mifflin St. Joer). CONCLUSION: Indirect calorimetry measurements that utilize the 5-min SS approach to estimate REE are considered the gold-standard. Under circumstances of non-SS, it appears 4-min and 3-min SS periods, or fixed time intervals of atleast 5 min are accurate and practical alternatives for estimating REE in adults with overweight and obesity. However, future trials should validate alternative methods in similar populations to confirm these findings.

Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model of Dopamine Transporter Deficiency Syndrome.

Dopamine Transporter Deficiency Syndrome (DTDS) is a rare autosomal recessive disorder caused by loss-of-function mutations in dopamine transporter (DAT) gene, leading to severe neurological disabilities in children and adults. DAT-Knockout (DAT-KO) mouse is currently the best animal model for this syndrome, displaying functional hyperdopaminergia and neurodegenerative phenotype leading to premature death in ~36% of the population. We used DAT-KO mouse as model for DTDS to explore the potential utility of a novel combinatorial adeno-associated viral (AAV) gene therapy by expressing DAT selectively in DA neurons and terminals, resulting in the rescue of aberrant striatal DA dynamics, reversal of characteristic phenotypic and behavioral abnormalities, and prevention of premature death. These data indicate the efficacy of a new combinatorial gene therapy aimed at rescuing DA function and related phenotype in a mouse model that best approximates DAT deficiency found in DTDS.

Prepuberal intranasal dopamine treatment in an animal model of ADHD ameliorates deficient spatial attention, working memory, amino acid transmitters and synaptic markers in prefrontal cortex, ventral and dorsal striatum.

Intranasal application of dopamine (IN-DA) has been shown to increase motor activity and to release DA in the ventral (VS) and dorsal striatum (DS) of rats. The aim of the present study was to assess the effects of IN-DA treatment on parameters of DA and excitatory amino acid (EAA) function in prepuberal rats of the Naples high-excitability (NHE) line, an animal model for attention-deficit hyperactivity disorder (ADHD) and normal random bred (NRB) controls. NHE and NRB rats were daily administered IN-DA (0.075, 0.15, 0.30 mg/kg) or vehicle for 15 days from postnatal days 28-42 and subsequently tested in the Làt maze and in the Eight-arm radial Olton maze. Soluble and membrane-trapped L-glutamate (L-Glu) and L-aspartate (L-Asp) levels as well as NMDAR1 subunit protein levels were determined after sacrifice in IN-DA- and vehicle-treated NHE and NRB rats in prefrontal cortex (PFc), DS and VS. Moreover, DA transporter (DAT) protein and tyrosine hydroxylase (TH) levels were assessed in PFc, DS, VS and mesencephalon (MES) and in ventral tegmental area (VTA) and substantia nigra, respectively. In NHE rats, IN-DA (0.30 mg/kg) decreased horizontal activity and increased nonselective attention relative to vehicle, whereas the lower dose (0.15 mg/kg) increased selective spatial attention. In NHE rats, basal levels of soluble EAAs were reduced in PFc and DS relative to NRB controls, while membrane-trapped EAAs were elevated in VS. Moreover, basal NMDAR1 subunit protein levels were increased in PFc, DS and VS relative to NRB controls. In addition, DAT protein levels were elevated in PFc and VS relative to NRB controls. IN-DA led to a number of changes of EAA, NMDAR1 subunit protein, TH and DAT protein levels in PFc, DS, VS, MES and VTA, in both NHE and NRB rats with significant differences between lines. Our findings indicate that the NHE rat model of ADHD may be characterized by (1) prefrontal and striatal DAT hyperfunction, indicative of DA hyperactivty, and (2) prefrontal and striatal NMDA receptor hyperfunction indicative of net EAA hyperactivty. IN-DA had ameliorative effects on activity level, attention, and working memory, which are likely to be associated with DA action at inhibitory D2 autoreceptors, leading to a reduction in striatal DA hyperactivity and, possibly, DA action on striatal EAA levels, resulting in a decrease of striatal EAA hyperfunction (with persistence of prefrontal EAA hyperfunction). Previous studies on IN-DA treatment in rodents have indicated antidepressant, anxiolytic and anti-parkinsonian effects in relation to enhanced central DAergic activity. Our present results strengthen the prospects of potential therapeutic applications of intranasal  DA by indicating an enhancement of selective attention and working memory in a deficit model.